Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals

Jaewon Lee, Tianxiang Zhang, Ilwoong Hwang, Ahrom Kim, Larissa Nitschke, Min Jae Kim, Jeannine M. Scott, Yosuke Kamimura, Lewis L. Lanier, Sung Jin Kim

Research output: Contribution to journalArticle

251 Scopus citations

Abstract

Long-lived "memory-like" NK cells have been identified in individuals infected by human cytomegalovirus (HCMV), but little is known about how the memory-like NK cell pool is formed. Here, we have shown that HCMV-infected individuals have several distinct subsets of memory-like NK cells that are often deficient for multiple transcription factors and signaling proteins, including tyrosine kinase SYK, for which the reduced expression was stable over time and correlated with epigenetic modification of the gene promoter. Deficient expression of these proteins was largely confined to the recently discovered FcRγ-deficient NK cells that display enhanced antibody-dependent functional activity. Importantly, FcRγ-deficient NK cells exhibited robust preferential expansion in response to virus-infected cells (both HCMV and influenza) in an antibody-dependent manner. These findings suggest that the memory-like NK cell pool is shaped and maintained by a mechanism that involves both epigenetic modification of gene expression and antibody-dependent expansion.

Original languageEnglish (US)
Pages (from-to)431-442
Number of pages12
JournalImmunity
Volume42
Issue number3
DOIs
StatePublished - Mar 17 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Lee, J., Zhang, T., Hwang, I., Kim, A., Nitschke, L., Kim, M. J., Scott, J. M., Kamimura, Y., Lanier, L. L., & Kim, S. J. (2015). Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals. Immunity, 42(3), 431-442. https://doi.org/10.1016/j.immuni.2015.02.013